title: Docetaxel-loaded nanoparticles based on star-shaped mannitol-core PLGA-TPGS diblock copolymer for breast cancer therapy.
abstract: A star-shaped biodegradable polymer, mannitol-core poly(d,l-lactide-co-glycolide)-d-α-tocopheryl polyethylene glycol 1000 succinate (M-PLGA-TPGS), was synthesized in order to provide a novel nanoformulation for breast cancer chemotherapy. This novel copolymer was prepared by a core-first approach via three stages of chemical reaction, and was characterized by nuclear magnetic resonance, gel permeation chromatography and thermogravimetric analysis. The docetaxel-loaded M-PLGA-TPGS nanoparticles (NPs), prepared by a modified nanoprecipitation method, were observed to be near-spherical shape with narrow size distribution. Confocal laser scanning microscopy showed that the uptake level of M-PLGA-TPGS NPs was higher than that of PLGA NPs and PLGA-TPGS NPs in MCF-7 cells. A significantly higher level of cytotoxicity was achieved with docetaxel-loaded M-PLGA-TPGS NPs than with commercial Taxotere®, docetaxel-loaded PLGA-TPGS and PLGA NPs. Examination of the drug loading and encapsulation efficiency proved that star-shaped M-PLGA-TPGS could carry higher levels of drug than linear polymer. The in vivo experiment showed docetaxel-loaded M-PLGA-TPGS NPs to have the highest anti-tumor efficacy. In conclusion, the star-like M-PLGA-TPGS copolymer shows potential as a promising drug-loaded biomaterial that can be applied in developing novel nanoformulations for breast cancer therapy.
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, People's Republic of China; Center for Biotech and Bio-Medicine, The Shenzhen Key Lab of Gene and Antibody Therapy and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tao
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zeng
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Wang
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Xiong
authors.forename: Chunping
authors.initials: C
authors.lastname: Ouyang
authors.forename: Laiqiang
authors.initials: L
authors.lastname: Huang
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002152:Calorimetry, Differential Scanning; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D003374:Coumarins / Q000494:pharmacology; D000077143:Docetaxel; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D008353:Mannitol / Q000737:chemistry*; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D011100:Polyglycolic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D055672:Static Electricity; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use*; D013818:Thermogravimetry; D013844:Thiazoles / Q000494:pharmacology; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D043823:Taxoids; D013844:Thiazoles; C517282:coumarin 6; D014810:Vitamin E; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008353:Mannitol; D011092:Polyethylene Glycols; C014225:tocophersolan
keywords: Docetaxel; Drug delivery; Nanoparticles; Nanotechnology for cancer therapy; Star-shaped copolymer